Human T-cell lymphotropic virus types I and II (HTLV-I/-II) are genetically related oncornaviruses that share modes of transmission (breast feeding, sexual, and parenteral). HTLV-I is important in the etiology of cancer and other diseases, while HTLV-II's role in disease is uncertain. VEB has been instrumental in defining the epidemiology of these viruses. In the United States, 7841 intravenous drug users were found to have very high HTLV-II seroprevalence (17% of females and 21% of males) and considerable HTLV-I seroprevalence (3.5%). HTLV-II seroprevalence was significantly increased for older, non-white, female, and HIV-infected subjects. In non-drug using Native American populations, HTLV-II seroprevalence in the Guaymi Indians of Panama was 9.5% and strongly associated with older age and with indicators of sexual and mother-to-child transmission. High HTLV-II seroprevalence in Brazilian Indians was found to persist for more than one generation, despite marked changes in lifestyle. Molecular sequencing identified two HTLV-II subtypes with regional variation but no clear disease associations. HTLV-I, unlike HTLV-II, is strongly linked to adult T-cell leukemia/lymphoma (ATL), a highly fatal non-Hodgkin's lymphoma. In Jamaica and Trinidad, two HTLV-I endemic areas, non-Hodgkin's lymphoma incidence (per 100,000 person-years) was 75 with HTLV-I infection during childhood, compared to 24 for all HTLV-I carriers and 2.2 for the general population. These findings support the hypothesis that early life HTLV-I infection greatly increases lymphoma risk. Similarly, VEB's family study noted that 12/12 mothers of ATL patients were infected with HTLV-I, compared to only 3/11 of mothers of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. These studies indicate that interruption of mother-to-child HTLV-I transmission would reduce ATL incidence decades in the future. VEB's current studies focus on understanding the natural history of HTLV-I/-II infection, especially the host, viral, and environmental interactions that increase the risk of progression from subclinical HTLV-I infection to ATL.